Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

A Phase II Study of Gleevec (Imatinib Mesylate, NSC 716051 Formerly STI571) in Children With Refractory or Relapsed Solid Tumors

Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have relapsed or refractory solid tumors of childhood. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Study Overview

• Status: Completed
• Conditions: Lung Metastases; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Gastrointestinal Stromal Tumor; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Childhood Synovial Sarcoma; Childhood Desmoplastic Small Round Cell Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: imatinib mesylate

Detailed Description

OBJECTIVES:

I. Determine the response rate of patients with relapsed or refractory pediatric solid tumors treated with imatinib mesylate.

II. Determine the toxicity of this drug in these patients. III. Determine the time to progression in patients treated with this drug. IV. Determine the pharmacokinetics of this drug in these patients. V. Correlate response with c-kit and platelet-derived growth factor receptor expression in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma/primitive neuroectodermal tumor vs osteosarcoma vs neuroblastoma vs other).

Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed solid tumors including the following:

  • Ewing's sarcoma
  • Bone or soft tissue primitive neuroectodermal tumor
  • Osteosarcoma
  • Neuroblastoma
  • Desmoplastic small round cell tumor
  • Synovial cell sarcoma
  • Gastrointestinal stromal tumor (GIST)

• Metastatic pulmonary disease eligible

  • No pleural effusion of any size or definite radiologic evidence of pleural-based disease

• Recurrent or refractory to conventional therapy

  • GIST eligible at initial presentation
• Tumor tissue blocks must be available

• At least 1 measurable lesion

  • At least 20 mm by conventional techniques
  • At least 10 mm by spiral CT scan
  • Lesions assessable only by radionuclide scan are not considered measurable
• Performance status - Lansky 50-100% (≤ 10 years of age)
• Performance status - Karnofsky 50-100% (> 10 years of age)
• At least 2 months
• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 75,000/mm^3* (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL* (RBC transfusions allowed)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN
• INR < 1.5
• PTT ≤ ULN
• Fibrinogen ≥ lower limit of normal
• Creatinine normal for age
• Glomerular filtration rate ≥ 70 mL/min
• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• At least 1 week since prior biologic therapy or immunotherapy and recovered
• At least 1 week since prior growth factors
• No concurrent immunomodulating agents
• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy
• No concurrent steroids
• Recovered from prior radiotherapy
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of pelvis
• At least 6 weeks since other prior substantial bone marrow radiation
• No concurrent radiotherapy during first course of treatment
• Concurrent palliative radiotherapy to local painful lesions allowed after first course of treatment provided there is no evidence of disease progression and at least 1 measurable lesion remains outside radiation port
• No concurrent therapeutic doses of warfarin
• No concurrent anticonvulsants that induce the cytochrome p450 enzyme system (e.g., phenytoin, carbamazepine, and phenobarbital)
• Concurrent benzodiazepines and gabapentin allowed
• Concurrent low-molecular weight heparin allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (imatinib mesylate); Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: imatinib mesylate; Given orally; Other Names: Gleevec; CGP 57148; Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate, determined using the RECIST criteria	95% confidence interval will be computed.	Up to 2 years
Toxicity reported using the CTC version 2.0		Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to disease progression	Calculated by the method of Kaplan and Meier.	Up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mason Bond, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: February 14, 2002
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimate): May 7, 2003

Study Record Updates

• Last Update Posted (Estimate): April 15, 2015
• Last Update Submitted That Met QC Criteria: April 14, 2015
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms; Sarcoma; Recurrence; Sarcoma, Ewing; Gastrointestinal Stromal Tumors; Osteosarcoma; Neuroblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma, Synovial; Desmoplastic Small Round Cell Tumor; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: NCI-2012-01869 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA098543 (U.S. NIH Grant/Contract); CDR0000069187; COG-ADVL0122; ADVL0122 (Other Identifier: CTEP)